Lifeboat Foundation

To create cultured LMNs that replicate ALS neuron physiology and function, the Japanese team combined a small molecule-based approach with transcription factor transduction. The researchers achieved 80% induction efficiency of LMNs within just two weeks compared with conventional methods.

The resulting LMNs were found to have replicated ALS-specific pathologies, such as the abnormal aggregation of TDP-43 and FUS proteins. The team confirmed functionality of the LMNs using a multi-electrode array (MEA) system to measure firing activity and network activity, which were found to be similar to mature neurons.

Further analysis of the cultured LMNs showed that in addition to maintaining ALS cellular markers, the LMNs had reduced survival rates compared with healthy cells, mimicking ALS motor neuron responses.